Piperazine → 8-Methyl-2-piperazin-1-ylmethyl-2,3-dihydro[1,4]dioxino[2,3-f]quinoline

HRID 860013Notes

Reaction equation

HRID 860013 reaction equation
[CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]3[O:15][CH2:14][C@H:13]([CH2:16]OS(C4C=CC(Br)=CC=4)(=O)=O)[O:12][C:8]3=2)[N:3]=1.[NH:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1.C(=O)(O)[O-].[Na+]>CS(C)=O>[CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]3[O:15][CH2:14][CH:13]([CH2:16][N:28]4[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]4)[O:12][C:8]3=2)[N:3]=1

Participants

5

Reactant 3

HCID 4837PiperazineHCID 516892Sodium BicarbonateHCID 20624762[(2R)-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl]methyl4-bromobenzenesulfonate

Product 1

HCID 696050258-Methyl-2-piperazin-1-ylmethyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolineYield 82%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of [(2R)-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl]methyl-4-bromobenzene sulfonate (1.35 g, 3 mmol) and piperazine (2.58 g, 30 mmol) in dimethylsulfoxide (16 mL) is heated at 75° C. under nitrogen for 1 hour, cooled and poured into saturated aqueous sodium bicarbonate. The mixture is extracted with ethyl acetate and the extracts are dried over anhydrous magnesium sulfate and evaporated to dryness. The residue is flash chromatographed on silica gel Merck-60 using a gradient of methanol (5–25%) in dichloromethane containing 0.2% ammonium hydroxide to provide the title compound as an off-white oil (0.736 g) identical to the compound of example 1B, step B′.

Workup

  1. temperaturecooled
  2. extractionThe mixture is extracted with ethyl acetate
  3. dry with materialthe extracts are dried over anhydrous magnesium sulfate
  4. customevaporated to dryness
  5. customchromatographed on silica gel Merck-60

Sources & evidence

ORD record
ord-4e16f9c37a774cb5adc9d1ffda09405d
Source dataset
uspto-grants-2006_12
Patent number
US07153849B2

Reaction notes

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